Adult Kidney Transplant Recipients Research Articles

210. Neutropenia and Associated Infectious Complications Among Kidney Transplant Recipients Receiving Valganciclovir Prophylaxis in the United States: An Administrative Claims Database Study

Abstract Background Valganciclovir (VGCV) prophylaxis is commonly utilized to prevent cytomegalovirus (CMV) infection among high (D+/R-) and intermediate (R+) risk kidney transplant recipients (KTRs). Due to the myelosuppressive effects of VGCV, KTRs may be at an increased risk of opportunistic infections (OIs) resulting in interruptions to VGCV therapy. Therefore, we aimed to quantify the clinical burden of neutropenia among adult KTRs receiving VGCV prophylaxis. Methods A retrospective cohort design was utilized to identify adult KTRs who received VGCV prophylaxis using the IBM MarketScan Commercial and Medicare Supplemental claims databases. First-time KTRs between 1/1/2012 - 12/31/2018 with 1 year of continuous pharmacy and medical coverage before (baseline period) and after (follow-up period) were included. KTRs with a History of other solid organ transplantation were excluded. Fills of ≥ 1 prescription of VGCV (either 450 mg or 900 mg/day) within 30 days of the kidney transplant (KT). Neutropenia events were identified as either ≥ 1 inpatient, or ≥ 2 outpatient ICD-9/ICD-10 diagnoses codes within 14 days. Results Of the 4,965 adults KTRs with baseline and follow-up enrollment, 3,258 (66%) used VGCV prophylaxis. 311/3256 (9.5%) developed neutropenia within 1-year post KT. Baseline characteristics were similar between those with and without neutropenia (table 1). The majority received the following pre-transplant immunosuppression: tacrolimus (78.9%), mycophenolate mofetil (62.8%) and steroids (prednisone, 79.3%, methylprednisolone 10.6%). KTRs with neutropenia had a nearly two-fold increase in the development of CMV infection compared to those without neutropenia. In addition, KTRs with neutropenia had significantly higher rate of bacterial or fungal infections compared to those without neutropenia (Table 2). Interruptions in VGCV prophylaxis (gap >15 days) were more common in KTRs with neutropenia (P< 0.001). Conclusion Our findings showed that neutropenia was associated viral, bacterial, and fungal OIs among adults KT receiving VGCV prophylaxis. The findings highlight the needs for interventions to reduce neutropenia and its associated OIs. These results suggest that clinical management steps to reduce rates of neutropenia among KT recipients may warrant further study. Disclosures Vladimir Turzhitsky, PhD, Merck & Co., Inc.,: Employee|Merck & Co., Inc.,: Stocks/Bonds Amit D. Raval, PhD, Merck and Co., Inc.: Employee of Merck|Merck and Co., Inc.: Stocks/Bonds Pamela Moise, PharmD, Merck & Co., Inc: Employee & Shareholder Sanjay Merchant, PhD, Merck & Co., Inc.: Stocks/Bonds.

509. Role of cell-mediated immune monitoring using Interferon-γ Enzyme-linked Immunosorbent Spot Assay to predict CMV infection within six months after kidney transplantation

Abstract Background CMV infection can cause substantial morbidity and mortality in kidney transplant (KT) recipients due to an impairment in cell-mediated immunity (CMI) from immunosuppressive drugs. We investigated the role of CMI monitoring prior to and after transplant to predict CMV infection after KT. Methods A prospective study was performed between December 2020 and December 2021. All adult KT recipients underwent CMI measurement by investigating IFN-γ-producing T cells using enzyme-linked immunosorbent (ELISpot) assay before and one month post-transplant. The incidence of CMV infection within six months after transplant was reported, and predictors of CMV infection were analyzed using the Cox proportional hazard model. Results We included 93 KT recipients with a mean (SD) age of 44 (11) years; 59.1% were male, and 98.9% were CMV seropositivity. Twenty-two (23.7%) participants received anti-thymocyte globulin (ATG) for induction therapy. A median (IQR) of IFN-γ-producing T cells measured one month after transplant was significantly lower compared to before transplant (148 [54-389] vs. 763 [409-1,067] SFUs per 2.5 x 105 PBMCs, p < 0.001). Forty (42.9%) KT recipients who developed CMV infection appeared to have significantly less IFN-γ-producing T cells compared to those did not develop CMV infection (47.1%) (115 [33-237] vs. 238[76-492] SFUs/2.5x105 PBMCs, p=0.019). In univariate analysis, predictors for CMV infection included higher panel-reactive antibody (HR 1.02 [95%CI, 1.01-1.03], p< 0.001), receiving ATG for induction therapy (HR 3.45 [95%CI, 1.82-6.56], < 0.001) and lack of CMI one month after transplant defined as IFN-γ-producing T-cells of < 250 SFUs/2.5x105 PBMCs (HR 3.11 [95%CI, 1.36-7.10], p=0.007). In multivariate analysis, lack of CMI one month after transplant is the only predictor which remained independently associated with CMV infection (HR 3.1 [95%CI 1.2-7.80], p=0.019) (Table 1). Conclusion KT recipients with low IFN-γ-producing T cell responses are more likely to develop CMV infection post-transplant. Quantification of CMI using ELISpot assay could potentially predict those at risk of CMV infection after KT. Disclosures All Authors: No reported disclosures.

LB2307. Safety and Efficacy of Letermovir (LET) versus Valganciclovir (VGCV) for Prevention of Cytomegalovirus (CMV) Disease in Kidney Transplant Recipients (KTRs): A Phase 3 Randomized Study

Abstract Background VGCV is approved for prophylaxis in adult KTRs at high risk for CMV disease (donor CMV-seropositive/recipient CMV-seronegative [D+/R-]); however, its use is limited by myelosuppression. LET is non-myelotoxic, does not require dose modification in renal impairment, and is approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic hematopoietic stem cell transplant recipients. This randomized, double-blind, Phase 3 non-inferiority study (NCT03443869; MK-8228-002) evaluated CMV prophylaxis with LET vs. VGCV in adult CMV D+/R- KTRs. Methods Adult CMV D+/R- KTRs were randomized 1:1 within 7 days post-kidney transplant (KT) to receive either LET 480 mg QD (PO/IV) with acyclovir (400 mg PO BID, adjusted for renal function), or VGCV (900 mg PO QD, adjusted for renal function), through Week 28 post-KT and followed up through Week 52 post-KT. Randomization was stratified by use of lymphocyte-depleting induction immunosuppression. The primary endpoint was the proportion of participants (pts) with CMV disease adjudicated by blinded committee through Week 52 post-KT (non-inferiority margin,10%). Results A total of 601 pts were randomized; 589 received ≥ 1 dose of study medication (median age [range], 51 [18–82] years; male, 72%; Black/African American, 9%; deceased donor, 60%; received lymphocyte-depleting induction immunosuppression, 46%), of whom two had detectable CMV viral DNA on Day 1 and one was CMV R+ (full analysis set, 586 pts). The proportion of pts with CMV disease through Week 52 post-KT was 10.4% with LET vs. 11.8% with VGCV (stratum-adjusted treatment difference, -1.4% [95% CI -6.5, 3.8]; Table 1). Drug-related adverse events (AEs) were reported in 19.9% of pts with LET and 35.0% of pts with VGCV through Week 28 post-KT. The rate of discontinuations due to an AE was 4.1% in the LET arm and 13.5% in the VGCV arm (Table 2). The incidence of neutropenia (absolute neutrophil count < 1000/µL) during the treatment phase was lower with LET than with VGCV (4.1% vs. 19.5%; difference, -15.4% [95% CI -20.7, -10.5]). Conclusion The study met its primary endpoint: LET was non-inferior to VGCV in preventing CMV disease in high-risk (CMV D+/R-) KTRs through Week 52 post-KT, and led to a lower rate of myelotoxicity than VGCV. Disclosures Ajit P. Limaye, MD, AiCuris: Advisor/Consultant|MedPace: Data Safety Monitoring Boards|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Novartis: Data Safety Monitoring Boards|Sana: Advisor/Consultant Klemens Budde, MD, Abbvie: Grant/Research Support|Abbvie: Honoraria|Alexion: Grant/Research Support|Alexion: Honoraria|Astellas: Grant/Research Support|Astellas: Honoraria|Bristol Myers Squibb: Grant/Research Support|Bristol Myers Squibb: Honoraria|Chiesi: Grant/Research Support|Chiesi: Honoraria|CSL Behring: Grant/Research Support|CSL Behring: Honoraria|Fresenius: Grant/Research Support|Fresenius: Honoraria|Hansa: Grant/Research Support|Hansa: Honoraria|Hexal: Grant/Research Support|Hexal: Honoraria|Hookipa Biotech: Grant/Research Support|Hookipa Biotech: Honoraria|Merck Sharp & Dohme: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Novartis: Grant/Research Support|Novartis: Honoraria|Otsuka: Grant/Research Support|Otsuka: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Roche: Grant/Research Support|Roche: Honoraria|Sandoz: Grant/Research Support|Sandoz: Honoraria|Shire: Grant/Research Support|Shire: Honoraria|Siemens: Grant/Research Support|Siemens: Honoraria|Takeda: Grant/Research Support|Takeda: Honoraria|Veloxis: Grant/Research Support|Veloxis: Honoraria|Vitaeris: Grant/Research Support|Vitaeris: Honoraria Atul Humar, MD, MSc, FRCPC, Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support|Takeda: Advisor/Consultant Julia Garcia-Diaz, MD, Astellas Pharma US, Inc.: Advisor/Consultant|Astellas Pharma US, Inc.: Speaker's Bureau Robert P. Carroll, BM BCh (Oxon), FRACP, DM (Oxon), Bristol Myers Squibb: Grant/Research Support|HANSA Biopharma: Advisor/Consultant Yoshihiko Murata, MD, PhD, Former employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Valerie L. Teal, MS, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Current Employee|Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Christopher L. Gilbert, n/a, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.,: Stocks/Bonds Barbara A. Haber, MD, Current employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co.,: Stocks/Bonds.

Predicting Kidney Transplant Recipient Cohorts’ 30-Day Rehospitalization Using Clinical Notes and Electronic Health Care Record Data

Rehospitalization after kidney transplant is costly to patients and health care systems and is associated with poor outcomes. Few prediction model studies have examined whether inclusion of clinical notes data from the electronic medical record (EMR) enhances prediction of rehospitalization. In a retrospective, observational study of first-time, adult kidney transplant recipients at a large, urban hospital in southeastern United States (2005-2015), we examined 30-day rehospitalization (30DR) using structured EMR and unstructured (i.e., clinical notes) data. We used natural language processing (NLP) methods on 8 types of clinical notes and included terms in predictive models using unsupervised machine learning approaches. Both the area under the receiver operating curve and precision-recall curve (ROC and PRC, respectively) were used to determine and compare model accuracy, and 5-fold cross-validation tested model performance. Among 2060 kidney transplant recipients, 30.7% were readmitted within 30 days. Predictive models using clinical notes did not meaningfully improve performance over previous models using structured data alone (ROC 0.6821; 95% confidence interval [CI]: 0.6644, 0.6998). Predictive models built using solely clinical notes performed worse than models using both clinical notes and structured data. The data that contributed to the top performing models were not identical but both included structured data and progress notes (ROC 0.6902; 95% CI: 0.6699, 0.7105). Including new features from clinical notes in risk prediction models did not substantially increase predictive accuracy for 30DR for kidney transplant recipients. Future research should consider pooling data from multiple institutions to increase sample size and avoid overfitting models.

Population pharmacokinetics of subcutaneous alemtuzumab in kidney transplantation.

Alemtuzumab is a monoclonal antibody used as induction immunosuppressive therapy in kidney transplantation. It targets CD52 on lymphocytes, inducing profound immune cell depletion upon administration. Owing to its off-label status in kidney transplantation, its pharmacokinetic characteristics are largely unknown in this setting, and its current fixed dosing algorithm originates from other populations. We developed a population pharmacokinetic model for alemtuzumab in kidney transplant recipients and investigated the potential of personalized alemtuzumab therapy. In total, 362 pharmacokinetic observations drawn 0-165 days after transplantation were available from 61 adult kidney transplant recipients who received two consecutive doses of 15 mg alemtuzumab subcutaneously. A population pharmacokinetic model was developed using nonlinear mixed-effects modelling and applied to simulate various dosing regimens. The alemtuzumab concentration-time data were best described by a two-compartmental model with first-order absorption and parallel first-order and time-varying concentration-dependent elimination, with between-subject variability on the first-order elimination (39.6%) and central distribution volume (39.6%). Alemtuzumab pharmacokinetics varied with body size, rendering lighter individuals exposed to lympholytic alemtuzumab concentrations (>0.1mg/L) for prolonged durations as compared to their heavier peers. This between-subject variability could be reduced through lean bodyweight-adjusted dosing, showing a twofold to threefold reduction in the slope of the median alemtuzumab exposure over the bodyweight range. Alemtuzumab displays substantial pharmacokinetic variability in kidney transplant recipients, which may warrant a personalized treatment strategy. Lean bodyweight-adjusted dosing poses an option for individualized dosing, but further evaluation of its potential clinical benefit is warranted.

Range and Consistency of Cardiovascular Outcomes Reported by Clinical Trials in Kidney Transplant Recipients: A Systematic Review.

A systematic review of all randomized controlled trials involving adult kidney transplant recipients that reported at least 1 cardiovascular outcome from January 2012 to December 2019 was performed, including Embase, MEDLINE, Cochrane, and ClinicalTrials.gov electronic databases. Trial characteristics were extracted and all levels of specification of the cardiovascular outcome measures reported were analyzed (the measure definition, metric' and method of aggregation). Measures assessing a similar aspect of cardiovascular disease were categorized into outcomes. From 93 eligible trials involving 27 609 participants, 490 outcome measures were identified. The outcome measures were grouped into 38 outcomes. A cardiovascular composite was the most common outcome reported (40 trials, 43%) followed by cardiovascular mortality (42%) and acute coronary syndrome (31%). Cardiovascular composite was also the most heterogeneous outcome with 77 measures reported followed by cardiovascular mortality (n = 58) and inflammatory biomarkers (n = 51). The most common cardiovascular composite outcome components reported were major cardiovascular events (18 trials), stroke unspecified (11 trials), and myocardial infarction unspecified (10 trials). There is substantial heterogeneity in cardiovascular outcome reporting in kidney transplant trials.

Pre-transplant hypoalbuminemia is not associated with worse short-term outcomes among kidney transplant recipients.

Serum albumin is an indicator of overall health status, but it remains unclear how pre-transplant hypoalbuminemia is associated with early post-transplant outcomes. This study included all adult kidney transplant recipients (KTRs) at our center from 01/01/2001-12/31/2017 with serum albumin measured within 30 days before transplantation. KTRs were grouped based on pretransplant albumin level normal (≥4.0g/dL), mild (≥3.5-<4.0g/dL), moderate (≥3.0-<3.5g/dL), or severe hypoalbuminemia (<3.0g/dL). Outcomes of interest included: length of hospital stay (LOS), readmission within 30 days, delayed graft function(DGF), and re-operation related to post-transplant surgical complications. We also analyzed rejection, graft failure, and death within 6 months post-transplant. A total of 2807 KTRs were included 43.6% had normal serum albumin, 35.3% mild, 16.6% moderate, and 4.5% severe hypoalbuminemia. Mild and moderate hypoalbuminemia were associated with a shorter LOS by 1.22 (p<0.001) and 0.80 days (p = 0.01), respectively, compared to normal albumin. Moderate (HR: 0.58; 95% CI: 0.37-0.91; p=0.02) and severe hypoalbuminemia (HR: 0.21; 95% CI: 0.07-0.68; p=0.01) were associated with significantly lower rates of acute rejection within 6 months post-transplant. Patients with pre-transplant hypoalbuminemia have post-transplant outcomes similar to those with normal serum albumin, but with a lower risk of acute rejection based on the degree of hypoalbuminemia.

Human papillomavirus infection-related cancer risk for kidney transplant recipients during adult life can be reduced by vaccination during childhood and adolescence.

Malignancies are found between the first three reasons of mortality in pediatric and adult kidney transplant recipients, who overall have disproportionately higher rates of cancer compared to the general population, including human papillomavirus (HPV)-related genital, anal and oropharynx region cancers. Therefore, preventing HPV in this patient population is extremely important. HPV-vaccine was demonstrated to prevent HPV infection in individuals with intact immune systems. In addition, recent data reported less precancerous HPV lesions and cervical cancers with use of HPV vaccine. Since HPV is a sexually transmitted virus that is typically acquired shortly after the onset of sexual activity, it is best to administer the HPV vaccine immunization prior to the onset of sexual activity. This article reviews the epidemiology and pathophysiology of the HPV infection, as well as its role in the development of HPV-related pre-cancerous lesions and cancers in both general population and kidney transplant recipients. The focus is on the most effective primary prophylactic strategy, which is the HPV vaccination. The particularities of HPV vaccination strategies in kidney transplant recipients are compared to the general population. In addition, the article analyzes the various causes of suboptimal HPV immunization rates in kidney transplant candidates and recipients and discusses vaccination optimization strategies that can be applied during childhood and adolescence to reduce the burden of HPV-related disease states and cancer among adult kidney transplant recipients.

Rejection and graft outcomes in kidney transplant recipients with and without angiotensin II receptor type 1 antibodies

AimAngiotensin II type 1 receptor antibody (AT1R Ab) is a non-Human Leucocyte Antigen (HLA) antibody that is maybe associated with early severe kidney transplant rejection and worse graft outcomes. This study aimed to assess the association between AT1R Ab and kidney transplant rejection and graft outcomes. MethodsWe performed a retrospective analysis of all adult kidney transplant recipients in an Australian centre who had an AT1R Ab test between 1 January 2015 to 30 June 2020. AT1R Ab positive patients were compared to AT1R Ab negative patients. Primary outcomes were rejection risk, type and histopathological severity scores. Secondary outcomes were 8-week graft function and graft loss. ResultsOf 965 kidney transplants that were performed during the study period, 73 patients had AT1R Ab tested; 16 (22%) were positive and 57(78%) were negative. Positive patients were on average younger and had higher level of donor-specific HLA antibodies. Rejection occurred in 13 (81%) positive patients and 41 (72%) negative patients (P = 0.45). No significant differences in rejection type or severity were found. HLA mismatch and peak panel reactive antibody ≥80%, but not AT1R Ab, independently predicted rejection. Average (132 vs. 177 mmol/L, P = 0.302) and graft loss were not significantly different between groups. ConclusionThe study found no evidence that AT1R Ab is associated with rejection type, severity or worse graft function. Future studies should assess its relationship with graft outcomes to help complement immunological risk assessment and potentially provide therapeutic options to alter outcomes.

Exercise training for adult kidney transplant recipients

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: This review aims: To assess the benefits and harms of regular physical activity interventions in adult kidney transplant recipients when compared with any other or no intervention. To determine whether benefits and harms vary in absolute or relative terms dependent on specific characteristics of the physical activity intervention (i.e. frequency, intensity, type, time, volume, progression and pattern of the intervention). To determine whether benefits and harms vary in absolute or relative terms dependent on specific characteristics of the participants studied (i.e. the influence of age and underlying kidney disease).

The effect of calcineurin inhibitors on anthropometric measurements in kidney transplant recipients

BackgroundThis study was designed to investigate the effect of calcineurin inhibitors (CNIs), cyclosporine (CsA), and tacrolimus (Tac) on anthropometrics in kidney transplant recipients.Methods111 of 128 adult kidney transplant recipients who received post-transplant CNIs were included in this retrospective study. Anthropometrics were recorded in the pre-transplant and post-transplant 4-year follow-up periods (1st, 3rd, 6th, 12th, 24th, 36th and 48th months).ResultsCompared to pre-transplant values, significant increases in body weight and body mass index (between 3rd and 48th months), waist and hip circumferences (between 1st and 48th months), waist-to-hip ratio (between 1st and 3rd or 6th months) and neck circumference (between 1st and 12th or 24th months) were observed in both CsA and Tac groups. A significant increase was noted in post-transplant body fat percentage values for the 3rd to 24th months in the CsA group, whereas for the 24th to 48th months in both CsA and Tac groups. Hip circumferences percentage changes from the pre-transplant period to the 1st, 12th and 24th months were significantly higher in CsA than in the Tac group. At each time point, there was no significant difference in percentage changes for other anthropometric parameters between the CsA and Tac groups. De novo diabetes mellitus developed in 8.3% of the CsA group and 19.1% of the Tac group.ConclusionsAfter a successful kidney transplant, anthropometric measurements increase in most recipients. Although the effect of calcineurin inhibitor type on weight gain is unclear, a regression analysis showed that CNI type was not a risk factor for the development of obesity in the 48th month. However, it is helpful to be cautious about its dyslipidemic effect in patients using CsA and the potential hazards of using Tac in patients with a diabetic predisposition.

Proteomic analysis of urinary extracellular vesicles of kidney transplant recipients with BKV viruria and viremia: A pilot study.

To better define the biological machinery associated with BK virus (BKV) infection, in kidney transplantation, we performed a proteomics analysis of urinary extracellular vesicles (EVs). Twenty-nine adult kidney transplant recipients (KTRs) with normal allograft function affected by BKV infection (15 with only viremia, 14 with viruria and viremia) and 15 controls (CTR, KTRs without BKV infection) were enrolled and randomly divided in a training cohort (12 BKV and 6 CTR) used for the mass spectrometry analysis of the EVs (microvesicles and exosomes) protein content and a testing cohort (17 BKV and 9 CTR) used for the biological validation of the proteomic results by ELISA. Bioinformatics and functional analysis revealed that several biological processes were enriched in BKV (including immunity, complement activation, renal fibrosis) and were able to discriminate BKV vs. CTR. Kinase was the only gene ontology annotation term including proteins less abundant in BKV (with SLK being the most significantly down-regulated protein). Non-linear support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) identified 36 proteins (including DNASE2, F12, AGT, CTSH, C4A, C7, FABP4, and BPNT1) able to discriminate the two study groups. The proteomic profile of KTRs with BKV viruria alone vs. viremia and viruria was quite similar. Enzyme-linked immunosorbent assay (ELISA) for SLK, BPNT1 and DNASE2, performed on testing cohort, validated proteomics results. Our pilot study demonstrated, for the first time, that BKV infection, also in the viruric state, can have a negative impact on the allograft and it suggested that, whether possible, an early preventive therapeutic strategy should be undertaken also in KTRs with viruria only. Our results, then, revealed new mechanistic insights into BKV infection and they selected potential biomarkers that should be tested in future studies with larger patients' cohorts.

Short and Long-Term Outcomes of Kidney Transplant Recipients Diagnosed With COVID-19 Infection: A Single-Center Observational Study.

Kidney transplant recipients (KTRs) are at an increased risk of severe disease and death caused by coronavirus disease 2019 (COVID-19) infection. There is a paucity of information on the evolution of graft function among hospitalized KTRs who overcome the infection. The study included adult KTRs at a single transplant institute who were diagnosed with COVID-19 and needed hospitalization between March 15, 2020, and January 15, 2021. We analyzed patient demographics, comorbid risk factors, and inpatient clinical courses for patients who were able to recover from the infection. Kidney function was analyzed pre-infection, during initial hospitalization, and up to 12 months post-infection. We identified 48 KTRs who were diagnosed with COVID-19 infection during the study period. Eighteen KTRs among these needed hospitalization for symptoms of fever and respiratory distress. Four patients died of COVID-19 infection-related complications and were excluded from the study. The 14 remaining patients in the study were predominantly of the Black race (85.7%), with a median time since transplant of four years. Of the patients,64.3% developed acute kidney injury (AKI), with an average peak serum creatinine (sCr) of 2.6 mg/dl and a glomerular filtration rate (GFR) of 35. The mean sCr and GFR of the group were 2 mg/dl and 44 at baseline (prior to infection). This represented an increase in their sCr and GFR of 34% and 29%, respectively. The median follow-up post-infection was 14.5 months. sCrand GFR were 1.87 mg/dl and 47 at three to six months, and 1.89 mg/dl and 48 at nine to 12 months post-infection. New onset proteinuria was noted in five out of 14 patients (36%), with complete resolution of the same in all at three to six months follow-up. Of patients with AKI,78% had complete recovery at three to six months follow-up. The mean baseline sCr and GFR of patients who had incomplete recovery was 2.35 and 31.5 with pre-existing proteinuria. Of our entire cohort, there was only one patient who experienced graft loss. This patient had a baseline sCr and GFR of 3.8 mg/dl and 22, existing proteinuria on urinalysis, and a history of biopsy-proven rejection. AKI is common among KTRs who are hospitalized with COVID-19 infection. Most of these recovered, although we noted that patients with baseline lower kidney function and existing proteinuria had a lower recovery rate.

Perspectives of Kidney Transplant Recipients on eHealth: Semistructured Interviews.

Face-to-face semistructured interviews were conducted with 30 adult kidney transplant recipients from New South Wales, Australia (urban and regional), in ambulatory clinics. We used purposive sampling to obtain a wide range of demographic and clinical characteristics. Transcripts were analyzed thematically. Ethics was approved by the Western Sydney Local Health District (6054-2019/ETH08718). Six themes were identified: seeking access to quality care (prioritizing and trusting clinician advice, better safety and timeliness, enabled by user-friendly content); supporting self-management (responsive to individualized informational need, empowerment through practical knowledge, encouraging connectedness); assessing reliability and trustworthiness (discerning information integrity, applying to own context, apprehensive about privacy and confidentiality); enhancing health system capabilities (synergy with routine consultations, essential to coordination, achieving goals by real-time monitoring); technology burden and limitation (uncertainty with navigation and comprehension, challenged by technical difficulties, requiring additional preparation, confrontation and distress); and lacking applicable value (diminished assurance of medical services, existing practice and procedures, hampered by low expectations and disinterest). Recipients felt eHealth could support healthcare delivery and self-management activities. However, they encountered challenges in navigating technology and were concerned about privacy, confidentiality, and misinformation. eHealth that is accessible, individualized, and secure may improve patient satisfaction and outcomes.

Hemorrhagic Pancreatitis in Pediatric Heart Transplant Recipients

Abstract Introduction/Objective Acute pancreatitis is a known side effect of tacrolimus in solid organ transplant recipients, but can be difficult to detect as symptoms may be vague and poorly localized, or overlap with the underlying condition. This phenomenon has most frequently been described in adult kidney transplant recipients. We present two autopsy cases in which pediatric patients with history of orthotopic heart transplantation both developed hemorrhagic pancreatitis shortly following operative procedures. Both had received immunosuppressants including tacrolimus during therapy. Although the etiology of pancreatitis in these medically complex cases is likely multifactorial, tacrolimus may be an important contributor. Methods/Case Report Case 1: A 6-year-old male with hypoplastic left heart syndrome was admitted for two years for medical management while awaiting transplant. Prior to and following transplantation he received immunosuppressants including tacrolimus to reduce risk of transplant rejection. Two weeks post-operatively, he developed abdominal pain and elevated pancreatic enzymes, leading to a diagnosis of pancreatitis. Imaging revealed hemorrhage. Tacrolimus was suspected to have caused this, and was discontinued. Despite medical management and multiple attempts to embolize vessels around the pancreas, the decedent remained unstable and ultimately went into hypotensive bradycardic cardiac arrest. Autopsy revealed a large hemorrhagic cavity confluent with a necrotic pancreas, as well as coagulum adherent to bowel loops throughout the abdomen. Case 2: A 13-year-old male status post two orthotopic heart transplants presented for a dental procedure. Following this, he developed an anaphylactic-type reaction to medication, with hives and bradycardia followed by cardiac arrest. He was resuscitated, however, his cardiac function steadily declined throughout the remainder of his stay. Heart biopsy revealed no evidence of cell-mediated transplant rejection. Pancreatic enzymes were mildly elevated, and abdominal imaging was unremarkable. His tacrolimus levels were noted to be supratherapeutic, and this was discontinued. Shortly before passing, he developed severe abdominal pain with distension, nausea and vomiting. At autopsy, he was found to have nearly two liters of hemorrhage and clot within the peritoneum emanating from a necrotic and hemorrhagic pancreas. Results (if a Case Study enter NA) NA. Conclusion Close clinical monitoring of pancreatic function should be considered in solid organ transplant recipients receiving tacrolimus.

Scope and Consistency of Cancer Outcomes Reported in Randomized Trials in Kidney Transplant Recipients

Cancer is an important outcome in kidney transplantation, but the scope and consistency of how cancer is defined and reported in trials involving kidney transplant recipients has not been evaluated. This study aimed to assess the range and variability of cancer outcomes in trials involving kidney transplant recipients. The ClinicalTrials.gov database was searched from February 2000 to July 2021 to identify all randomized controlled trials (RCTs) in adult kidney transplant recipients, and which included cancer as a specified outcome. The definition of cancer, types of cancer (if any), timepoint(s) of measurement and method of aggregation were extracted for each cancer outcome. Of the 819 trials in kidney transplantation, only 84 (10%) included 1 or more cancer outcomes. Of these, 72 of 84 (86%) trials included cancer as a secondary outcome and 12 of 84 (14%) considered cancer as a primary outcome. The most frequent description of cancer was "malignancy" (n= 44, 43%), without reference to diagnostic criteria, histology, grade, or stage. The 2 most common cancer types were posttransplant lymphoproliferative disorder (PTLD) (n= 20, 20%) and nonmelanoma skin cancer (n= 10, 10%). Several methods of aggregation were identified, including incidence or rate (n= 47, 46%), frequency or proportion (n= 30, 29%), and time to event (n= 5, 5%). Approximately half the cancer outcomes were measured at a single time point (n= 44, 52%). Cancer is an infrequently reported outcome and is inconsistently defined in trials of kidney transplant recipients. Consistent reporting of cancer outcomes using standardized definitions would provide important information on the impact of cancer in patients after kidney transplantation.

The association of venous thromboembolism with blood transfusion in kidney transplant patients.

Red blood cell transfusion (RBCT) is common after kidney transplantation and could have pro-thrombotic effects predisposing to venous thromboembolism (VTE). The risks for developing of VTE after RBCT in kidney transplant patients are unknown. This was a retrospective cohort study of adult kidney transplant recipients from 2002 to 2018. The exposure of interest was receipt of RBCT after transplant. Cox proportional hazards models were used to calculate hazard ratios (HR) for the outcomes of venous thromboembolism [VTE] (deep venous thrombosis [DVT] or pulmonary embolism [PE]) using RBCT as a time-varying, cumulative exposure. Out of 1258 kidney transplants recipients, 468 (37%) were transfused during the study period. Seventy-nine study participants (6.3%) developed VTE, 72 DVT (5.7%), and 22 PE (1.8%). For the receipt of 1, 2, 3-5, and >5 RBCT, compared to individuals never transfused, the number of events and adjusted HR (95%CI) for VTE were 6 (6.2%) HR 1.57 (0.69-3.58), 9 (7.6%) HR 2.54 (1.30-4.96), 15 (11.9%) HR 2.73 (1.38-5.41), and 23 (18.1%) HR 5.77 (2.99-11.14) respectively; for DVT, it was 6 (6.2%) HR 1.94 (0.84-4.48), 9 (7.6%) HR 2.92 (1.44-5.94), 14 (11.1%) HR 3.29 (1.63-6.65), and 21 (16.5%) HR 6.97 (3.53-13.76), respectively. For PE, among transfused individuals, there were 14 events (3.0%) and the HR was 2.40 (1.02-5.61). The risks for developing VTE, DVT, and PE were significantly increased in kidney transplant patients receiving RBCT after transplant. Receipt of RBCT should prompt considerations for judicious monitoring and assessment for thrombosis.

Fatal Case of Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient

Fatal Case of Epstein-Barr Virus-Negative Post-Transplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient

Symptomatic atherosclerotic vascular disease and graft survival in primary kidney transplant recipients – Observational analysis of the united network of organ sharing database

ObjectivesThe aim of this study was to investigate whether symptomatic atherosclerotic vascular disease (SAVD) was associated with graft survival in primary kidney transplant recipients. Summary background dataRecipient atherosclerotic vascular disease is associated with increased mortality rates amongst renal transplant patients. However, its relationship with graft survival has not been well studied. MethodsThis retrospective observational analysis was performed using data for adult kidney transplant recipients between 11/09/2000 and 28/02/2020 extracted from the UNOS national organ transplantation database. Patients were divided into two groups based on recipient history of symptomatic atherosclerotic disease (angina or peripheral vascular disease). Risk-adjusted outcomes were assessed by multivariate Cox regression analysis adjusting for both donor and recipient characteristics. Results11,771 adult kidney transplant recipients from the UNOS database were eligible for analysis (1543 had a history of SAVD, 10,228 did not have a history of SAVD). After adjusting for confounders, positive SAVD status was associated with an adverse effect on graft survival at both 1 year (HR 1.35, p < 0.001) and 10 years (HR 1.15, p < 0.001). ConclusionsSAVD should be considered an independent risk factor for poor prognosis in patients undergoing kidney transplant.

Navigating medication-taking after kidney transplant.

Mixed methods are valuable in understanding multifaceted health behaviors like medication adherence. Kidney transplant recipients (KTRs) have complex medication regimens and are more vulnerable to nonadherence relative to other transplant recipients. Yet mixed methods have not been widely applied to examine adherence among KTRs, especially in relation to prescribed medications beyond immunosuppressants. As part of a sequential approach, we used in-depth interviews to better understand findings from a previous quantitative study and to describe additional factors that influence prescription medication-taking among adult KTRs. Semi-structured interviews were conducted with a purposive sample of 14 adult KTRs recruited from a transplant center in Chicago, IL. Deductive and inductive content analysis was used to code transcripts and identify key themes. Across the sample, we identified insurance challenges, disruptions in routine, and poor mental well-being as barriers to adherence at the patient level. For Black and Hispanic KTRs, poor communication between providers and disjointed care transitions posed additional barriers at the health system level. Compared with White KTRs, Black and Hispanic KTRs experienced greater medication burden due to comorbidities, while medication and digital literacy challenges were unique to Hispanic KTRs. KTRs are often motivated to take medications as prescribed, but sometimes lack the capacity or support to do so. Eliciting KTR perspectives is necessary in addressing knowledge and resource gaps at the patient and health system levels to improve adherence. In addition, recognizing the relative burden of taking comorbidity medications compared with immunosuppressants may important, particularly for Black and Hispanic KTRs.